The following article is part of conference coverage from the 2019 American Academy of Neurology Annual Meeting (AAN 2019) in Philadelphia, PA. Neurology Advisor’s staff will be reporting breaking news associated with research conducted by leading experts in neurology. Check back for the latest news from AAN 2019.


PHILADELPHIA — Compared with placebo, eculizumab (Soliris®, Alexion Pharmaceuticals, Inc.) had a significantly lower risk of relapse in patients with anti-aquaporin-4 (AQP4) auto antibody-positive neuromyelitis optica spectrum disorder (NMOSD), according to a study presented at the 2019 American Academy of Neurology Annual Meeting, held May 4-10, 2019, in Philadelphia, and simultaneously published in the New England Journal of Medicine.1,2

Continue Reading

In this phase 3, randomized, double-blind, placebo-controlled, time-to-event trial (PREVENT; identifier: NCT01892345), patients from 70 sites in 18 countries were randomly assigned in a 2:1 ratio to receive either intravenous eculizumab or matched placebo. Patients received 900 mg of eculizumab weekly for the first 4 doses starting on day 1, followed by 1200 mg every 2 weeks starting at week 4, or a matched placebo.

The continued use of stable-dose immunosuppressive therapy was permitted, including those who received rituximab but not within 3 months before enrolling in the trial. Because of incompatibility between rituximab mechanism of action and that of the terminal complement inhibitor eculizumab, rituximab was not permitted as concomitant immunosuppressive therapy. Moreover, since eculizumab increases the risk for meningococcal and encapsulated bacterial infection by blocking the terminal complement system, all patients were vaccinated against Neisseria meningitidis before receiving eculizumab.

After the enrollment of 88 patients, the protocol was amended to create an independent relapse adjudication committee consisting of 2 neurologists and 1 neuro-ophthalmologist, who reviewed all physician-determined relapses.

The primary end point was the first adjudicated relapse. The original primary end point (physician-determined relapse) was changed to a sensitivity analysis. Secondary outcomes included the adjudicated annualized relapse rate, quality-of-life measures, and the score on the Expanded Disability Status Scale (EDSS).

Patients, site staff members, representatives of the sponsor, the independent relapse adjudication committee, and EDSS raters were unaware of the trial-group assignments, and trial agents and treatment kits were identical.

A total of 96 patients received eculizumab and 47 received placebo. Overall, 91% of the patients were women. At baseline, the mean (±SD) annualized relapse rate during the previous 24 months was 1.99±0.94. Adjudicated relapse occurred in 3% of patients in the eculizumab group and 43% in the placebo group (hazard ratio [HR], 0.06; 95% CI, 0.02-0.20; P <.001).

Related Articles

In the sensitivity analysis, relapses occurred in 15% in the eculizumab group and 62% in the placebo group (HR, 0.18; 95% CI, 0.10-0.34; P <.001). Of 45 physician-determined relapses overall, 24 (53%) were adjudicated as relapses. Despite this discordance, the sensitivity analysis also showed a significantly lower risk for relapse with eculizumab vs placebo.

The adjudicated annualized relapse rate was 0.02 in the eculizumab group and 0.35 in the placebo group (rate ratio, 0.04; 95% CI, 0.01-0.15; P <.001). The difference between groups for the other secondary end points was not significant.

There were higher rates of upper respiratory tract infection and headache reported in the eculizumab group vs placebo group. There was one death from pulmonary empyema in the eculizumab group.

Although the trial was stopped after 23 of 24 prespecified adjudicated relapses, researchers noted that it still retained at least 80% power to detect a between-group difference for the primary end point.

Researchers stressed that further study needs to be done to understand the long-term effect of eculizumab in patients with NMOSD, “since there was no significant between-group difference in measures of disability progression.”

Disclosure: Alexion Pharmaceuticals funded the PREVENT trial. They also designed the trial in consultation with two academic authors, provided the trial agents, and analyzed the data.

For more coverage of AAN 2019, click here.


1. Pittock SJ, Berthele A, Fujihara K, et al. Eculizumab in aquaporin-4-positive neuromyelitis optica spectrum disorder [published online May 3, 2019]. N Engl J Med. doi:10.1056/NEJMoa1900866

2. Pittock SJ, Berthele A, Fujihara K, et al. Efficacy and safety of eculizumab in aquaporin-4 antibody positive (AQP4-IgG+) neuromyelitis optica spectrum disorder (NMOSD): a phase 3, randomized, double-blind, placebo-controlled, multicenter trial (PREVENT). Presented at: 2019 American Academy of Neurology Annual Meeting; May 4-10, 2019; Philadelphia, PA. Abstract 009.

This article originally appeared on Neurology Advisor